Acupuncture therapy (AT) is a non-pharmacological method of treatment that has been applied to various neurological diseases. However, studies on its longitudinal effect on the neural mechanisms of patients with mild cognitive impairment (MCI) for treatment purposes are still lacking in the literature. In this clinical study, we assess the longitudinal effects of ATs on MCI patients using two methods: (i) Montreal Cognitive Assessment test (MoCA-K, Korean version), and (ii) the hemodynamic response (HR) analyses using functional near-infrared spectroscopy (fNIRS). fNIRS signals of a working memory (WM) task were acquired from the prefrontal cortex. Twelve elderly MCI patients and 12 healthy people were recruited as target and healthy control (HC) groups, respectively. Each group went through an fNIRS scanning procedure three times: The initial data were obtained without any ATs, and subsequently a total of 24 AT sessions were conducted for MCI patients (i.e., MCI-0: the data prior to ATs, MCI-1: after 12 sessions of ATs for 6 weeks, MCI-2: another 12 sessions of ATs for 6 weeks). The mean HR responses of all MCI-0–2 cases were lower than those of HCs. To compare the effects of AT on MCI patients, MoCA-K results, temporal HR data, and spatial activation patterns (i.e., t-maps) were examined. In addition, analyses of functional connectivity (FC) and graph theory upon WM tasks were conducted. With ATs, (i) the averaged MoCA-K test scores were improved (MCI-1, p = 0.002; MCI-2, p = 2.9e^–4); (ii) the mean HR response of WM tasks was increased (p < 0.001); and (iii) the t-maps of MCI-1 and MCI-2 were enhanced. Furthermore, an increased FC in the prefrontal cortex in both MCI-1/MCI-2 cases in comparison to MCI-0 was obtained (p < 0.01), and an increasing trend in the graph theory parameters was observed. All these findings reveal that ATs have a positive impact on improving the cognitive function of MCI patients. In conclusion, ATs can be used as a therapeutic tool for MCI patients as a non-pharmacological method (Clinical trial registration number: KCT 0002451 https://cris.nih.go.kr/cris/en/).

Parkinson’s disease (PD) leads to impaired mobility and limited independence. We investigated the effects of acupuncture on gait disturbance and analyzed hemodynamic changes caused by acupuncture in the cerebral cortex of patients with PD. Participants (n = 26) with gait disturbance due to PD were randomly assigned to the intervention (acupuncture twice a week for 4 weeks + conventional therapy) or control (conventional therapy) groups. We analyzed gait parameters using the GAITRite system and hemodynamic responses in the cerebral cortices using functional near-infrared spectroscopy, Unified Parkinson’s Disease Rating Scale (UPDRS) scores, neurotransmitter levels, as well as the immediate effects of acupuncture in patients with PD. The participants tended to walk with hypometric gait (high cadence, short steps) overground. After acupuncture treatment, those in the intervention group showed a significant reduction in cadence and the UPDRS scores involving “walking and balance” compared with those in the control group (P = .004 and P = .020, respectively); the stride, swing, and single support times were significantly increased (P = .006, P = .001, and P = .001, respectively). Oxyhemoglobin levels in the intervention group while walking on a treadmill were significantly increased in the prefrontal and supplementary motor areas. The oxyhemoglobin levels in the prefrontal cortex and swing time revealed significant positive correlations. Our findings indicated that acupuncture tended to improve hypometric gait and rearranged activation of the cerebral cortex. Thus, acupuncture may be a useful complementary treatment for gait disturbance, including hypometric gait, in patients with PD. Trial Registration Number. Clinical Research Information Service (KCT0002603), https://cris.nih.go.kr/cris/index.jsp

Microglial activation elicits an immune response by producing proinflammatory modulators and cytokines that cause neurodegeneration. Therefore, a plausible strategy to prevent neurodegeneration is to inhibit neuroinflammation caused by microglial activation. Myricetin, a natural flavanol, induces neuroprotective effects by inhibiting inflammation and oxidative stress. However, whether myricetin inhibits lipopolysaccharide (LPS)-induced neuroinflammation in hippocampus and cortex regions is not known. To test this, we examined the effects of myricetin on LPS-induced neuroinflammation in a microglial BV2 cell line. We found that myricetin significantly downregulated several markers of the neuroinflammatory response in LPS-induced activated microglia, including inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory modulators and cytokines such as prostaglandin E2 (PGE₂), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Moreover, myricetin suppressed the expression of c-Jun NH2-terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK), which are components of the mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, myricetin inhibited LPS-induced macrophages and microglial activation in the hippocampus and cortex of mice. Based on our results, we suggest that myricetin inhibits neuroinflammation in BV2 microglia by inhibiting the MAPK signaling pathway and the production of proinflammatory modulators and cytokines. Therefore, this could potentially be used for the treatment of neuroinflammatory diseases.

Almost half of mild cognitive impairment (MCI) patients progress to dementia, which is associated with decreased quality of life and obstacles to independent living. Relevant management is expected to prevent MCI patients from progressing to dementia. In recent years, electroacupuncture (EA) has been used to treat various kinds of neurological disorders including MCI. This study evaluates the use of EA for MCI patients to increase cognitive function through a comparison with Western medications. Randomized controlled trials (RCT) or systematical reviews (SR) of EA versus Western medications for MCI were searched using the following 10 databases: Pubmed, Cochrane Library, CINAHL, EMBASE, China National Knowledge Infrastructure (CNKI), National Digital Science Library (NDSL), Journal of Oriental Neuropsychiatry (JON), Korean Medical Database (KMBASE), KoreaMed, and OASIS, from October 2007 to August 2017, without language restriction. A methodological quality assessment of RCTs or SRs that met inclusion criteria was conducted using Cochrane Risk of bias (RoB) tool and a meta-analysis by RevMan (Review Manager) 5.3.5 version of Cochrane collaboration. Five RCTs with 257 patients met inclusion criteria and those were randomly divided into two groups: the EA group (n = 103) and Western medications group (n = 154). The methodological quality of the included studies showed high risk or/and unclear of risk of bias. The meta-analysis of five studies reported that the EA group was better than the Western medications group, improving the Mini Mental State Examination (MMSE) score by 0.65 [95% CI 0.28~1.01] higher mean difference, Montreal Cognitive Assessment (MoCA) score by 0.66 [95% CI 0.00~1.32] higher mean difference. Adverse effects were not reported in the selected studies. Electroacupuncture was an effective treatment for MCI patients by improving cognitive function. However, the included studies presented a low methodological quality and no adverse effects were reported. Thus, further comprehensive studies with a design in depth are needed to derive significant results.

The second most common progressive neurodegenerative disorder, Parkinson’s disease (PD), is characterized by a broad spectrum of symptoms that are associated with its progression. Several studies have attempted to classify PD according to its clinical manifestations and establish objective biomarkers for early diagnosis and for predicting the prognosis of the disease. Recent comprehensive research on the classification of PD using clinical phenotypes has included factors such as dominance, severity, and prognosis of motor and non-motor symptoms and biomarkers. Additionally, neuroimaging studies have attempted to reveal the pathological substrate for motor symptoms. Genetic and transcriptomic studies have contributed to our understanding of the underlying molecular pathogenic mechanisms and provided a basis for classifying PD. Moreover, an understanding of the heterogeneity of clinical manifestations in PD is required for a personalized medicine approach. Herein, we discuss the possible subtypes of PD based on clinical features, neuroimaging, and biomarkers for developing personalized medicine for PD. In addition, we conduct a preliminary clustering using gait features for subtyping PD. We believe that subtyping may facilitate the development of therapeutic strategies for PD.

Background: Mild cognitive impairment (MCI) is a symptom characterizing cognitive decline and a transitional state between normal aging and dementia; however, there is no definitive diagnosis and treatment for MCI. Neurofeedback (NF), which is a training mechanism that employs operant conditioning to regulate brain activity, has been increasingly investigated concerning its beneficial effects for dementia and MCI. Methods: This study investigated cognitive improvement and hemodynamic changes in the prefrontal cortex (PFC) following NF training in patients with MCI. Five patients with MCI received NF training for enhanced beta band activity in the dorsolateral PFC—16 sessions for 8 weeks—with each session divided into 9 5-minute trials. The primary outcome measure was a cognitive assessment tool: the Korean version of the Montreal Cognitive Assessment. The secondary outcome measures were the Central Nervous System Vital Signs for neurocognitive testing, hemodynamic changes using functional near-infrared spectroscopy in the PFC during a working-memory task, and Beck Depression Inventory scores. Results: After completing the training, patients’ cognitive function significantly improved in domains such as composite memory, cognitive flexibility, complex attention, reaction time, and executive function. Increased electroencephalogram beta power was observed over NF training sessions (Spearman rank correlation test: r = 0.746, P = .001). The threshold value for gaining positive feedback from pre-NF baseline on beta power significantly increased (Spearman rank correlation test: r = 0.805, P = .001). Hemodynamic response in PFC changed after NF training, and individual differences were identified. Specifically, hypoactivation of the hemodynamic response by emotional distraction recovered following NF training. Conclusion: We suggest that patients’ cognitive processing efficiency was improved by the NF training. These beneficial results suggest that NF training may have potential therapeutic applications to prevent the progression from MCI to dementia. Trial registration number: Clinical Research Information Service (KCT0003433).